Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury.

A Wirelessly Powered Scattered Neural Recording Wearable System.

This paper introduces a wirelessly powered scattered neural recording wearable system that can facilitate continuous, untethered, and long-term electroencephalogram (EEG) recording. The proposed system, including 32 standalone EEG recording devices and a central controller, is incorporated in a wearable form factor. The standalone devices are sparsely distributed on the scalp, allowing for flexible placement and varying quantities to provide extensive spatial coverage and scalability. Each standalone device featuring a low-power EEG recording application-specific integrated circuit (ASIC) wirelessly receives power through a 60 MHz inductive link. The low-power ASIC design (84.6 µW) ensures sufficient wireless power reception through a small receiver (Rx) coil. The 60 MHz inductive link also serves as the data carrier for wireless communication between standalone devices and the central controller, eliminating the need for additional data antennas. All these efforts contribute to the miniaturization of standalone devices with dimensions of 12×12×5 mm3, enhancing device wearability. The central controller applies the pulse width modulation (PWM) scheme on the 60 MHz carrier, transmitting user commands at 4 Mbps to EEG recording ASICs. The ASIC employs a novel synchronized PWM demodulator to extract user commands, operating signal digitization and data transmission. The analog frontend (AFE) amplifies the EEG signal with a gain of 45 dB and applies band-pass filtering from 0.03 Hz to 400 Hz, with an input-referred noise (IRN) of 3.62 µVRMS. The amplified EEG signal is then digitized by a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC) with a peak signal-to-noise and distortion ratio (SNDR) of 55.4 dB. The resulting EEG data is transmitted to an external software-defined radio (SDR) Rx through load-shift-keying (LSK) backscatter at 3.75 Mbps. The system's functionality is fully evaluated in human experiments.

Effects of BNT162b2 mRNA Covid-19 vaccine on vascular function.

The effects of Covid-19 vaccines on vascular function are still controversial. We evaluated the effects of BNT162b2 vaccine (BioNTech and Pfizer) on endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID). This study was a prospective observational study. A total of 23 medical staff at Hiroshima University Hospital were enrolled in this study. FMD and NID were measured before vaccination and two weeks and six months after the 2nd dose of vaccination. FMD was significantly smaller two weeks after the 2nd dose of vaccination than before vaccination (6.5±2.4% and 8.2±2.6%, p = 0.03). FMD was significantly larger at six months than at two weeks after the 2nd dose of vaccination (8.2±3.0% and 6.5±2.4%, p = 0.03). There was no significant difference between FMD before vaccination and that at six months after the 2nd dose of vaccination (8.2±2.6% to 8.2±3.0%, p = 0.96). NID values were similar before vaccination and at two weeks, and six months after vaccination (p = 0.89). The BNT162b2 Covid-19 vaccine temporally impaired endothelial function but not vascular smooth muscle function, and the impaired endothelial function returned to the baseline level within six months after vaccination.

Reconfiguration of low-voltage distributed power sources within electric power's distribution network based on improved particle swarm-fish swarm fusibility algorithm.

With the development of distributed power sources in the distribution network, the algorithm of distribution network reconfiguration is gaining attention from experts and scholars. Its goal is to reduce the power loss during power transmission, so as to reduce the power grid loss during power transmission. And weaken the electric heating effect in the process of electric energy transmission, thus maintaining the safety of the surrounding residents. Due to the wire impedance effect, a lot of electric energy of the circuit is lost to electric heating, which is easy to cause local overheating and lead to fire. This will not only cause power loss, but also endanger the safety of surrounding residents. To address the issue, experiments on distribution grid reconstruction are performed using the enhanced particle swarm-fish swarm algorithm with the Elecgrid self-constructed dataset. Initially, low-voltage distributed power sources in parallel are connected to the circuit, thereby decreasing internal resistance and electrical heat. Then, by controlling the circuit in the system, the double separation relay adjusts the inductance and capacitance of the conductor, thus reducing the reactance length. Additionally, particle swarm particles are mutated to enable them to jump out of the local optimum, and elite fish approach is used to expand the search area. Finally, the proposed fusion algorithm is applied to the self-built data set of Elecgrid and compared with the other three algorithms. The fusion algorithm serves as the standard test system for this comparison. The active power loss of the hybrid algorithm is 63 kW at an operating voltage of 0.74 V. The loss work of the other three algorithms is 74 kW, 97 kW and 109 kW respectively. The mixed algorithm has the lowest loss among the four algorithms. The experiments are repeated for six times, and the linear fitting degrees of the four algorithms are 0.9804, 0.9527, 0.9612 and 0.9503, respectively. The experimental results show that the application of this algorithm can effectively reduce the active loss in the process of distribution network reconfiguration, thus reducing energy consumption; At the same time, it can reduce the electric heating in the process of electric energy transmission, and then prevent the occurrence of fire. There are three main contributions of this study. Firstly, the resistance in the transmission path is reduced by using this algorithm, so that the power transmission efficiency can be analyzed more accurately. Secondly, the new algorithm enriches the power safety maintenance method; Finally, the fire caused by local overheating of the line is reduced by fusion algorithm.

A Wireless Multimodal Physiological Monitoring ASIC for Animal Health Monitoring Injectable Devices.

Utilizing injectable devices for monitoring animal health offers several advantages over traditional wearable devices, including improved signal-to-noise ratio (SNR) and enhanced immunity to motion artifacts. We present a wireless application-specific integrated circuit (ASIC) for injectable devices. The ASIC has multiple physiological sensing modalities including body temperature monitoring, electrocardiography (ECG), and photoplethysmography (PPG). The ASIC fabricated using the CMOS 180 nm process is sized to fit into an injectable microchip implant. The ASIC features a low-power design, drawing an average DC power of 155.3 µW, enabling the ASIC to be wirelessly powered through an inductive link. To capture the ECG signal, we designed the ECG analog frontend (AFE) with 0.3 Hz low cut-off frequency and 45-79 dB adjustable midband gain. To measure PPG, we employ an energy-efficient and safe switched-capacitor-based (SC) light emitting diode (LED) driver to illuminate an LED with milliampere-level current pulses. A SC integrator-based AFE converts the current of photodiode with a programmable transimpedance gain. A resistor-based Wheatstone Bridge (WhB) temperature sensor followed by an instrumentation amplifier (IA) provides 27-47 °C sensing range with 0.02 °C inaccuracy. Recorded physiological signals are sequentially sampled and quantized by a 10-bit analog-to-digital converter (ADC) with the successive approximation register (SAR) architecture. The SAR ADC features an energy-efficient switching scheme and achieves a 57.5 dB signal-to-noise-and-distortion ratio (SNDR) within 1 kHz bandwidth. Then, a back data telemetry transmits the baseband data via a backscatter scheme with intermediate-frequency assistance. The ASIC's overall functionality and performance has been evaluated through an in vivo experiment.

Geometric constraint-triggered collagen expression mediates bacterial-host adhesion.

Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.

Impact of multidisciplinary team on the pattern of care for brain metastasis from breast cancer.

Purpose: The aim of this study was to explore how a multidisciplinary team (MDT) affects patterns of local or systematic treatment. Methods: We retrospectively reviewed the data of consecutive patients in the breast cancer with brain metastases (BCBM) database at our institution from January 2011 to April 2021. The patients were divided into an MDT group and a non-MDT group. Results: A total of 208 patients were analyzed, including 104 each in the MDT and non-MDT groups. After MDT, 56 patients (53.8%) were found to have intracranial "diagnosis upgrade". In the matched population, patients in the MDT group recorded a higher proportion of meningeal metastases (14.4% vs. 4.8%, p = 0.02), symptomatic tumor progression (11.5% vs. 5.8%, p = 0.04), and an increased number of occurrences of brain metastases (BM) progression (p < 0.05). Attending MDT was an independent factor associated with ≥2 courses of intracranial radiotherapy (RT) [odds ratio (OR) 5.4, 95% confidence interval (CI): 2.7-10.9, p < 0.001], novel RT technique use (7.0, 95% CI 3.5-14.0, p < 0.001), and prospective clinical research (OR 5.7, 95% CI 2.4-13.4, p < 0.001). Conclusion: Patients with complex conditions are often referred for MDT discussions. An MDT may improve the qualities of intracranial RT and systemic therapy, resulting in benefits of overall survival for BC patients after BM. This encourages the idea that treatment recommendations for patients with BMBC should be discussed within an MDT.

Set of mathematical models for Bessel-Gauss beams coupling into the parabolic-index fiber under the influence of atmospheric turbulence and random jitter.

The expression of efficiency for Bessel-Gauss (BG) beams coupling into the parabolic fibers (PF) after passing through the Cassegrain antenna system is first derived. The effects of atmospheric turbulence and random jitter of the coupling lens on the efficiency are also taken into account to improve the practical applicability of our model. This article use a BG beam with a wavelength of 1550 mm and fiber with a core radius RF of 50 µm and a relative refractive index difference ζ of 0.01 for simulation testing. The optimal parameters of the antenna system are determined: the radius of the primary mirror and the secondary mirror is 8.33 cm and 1.25 cm, respectively. The coupling efficiency of BG beams of different orders reaches above 94% simultaneously when the lens's focal length is 7.8 cm. After taking into account the transmission efficiency of the antenna system, the system's total efficiency for BG beams of different orders averages 76.33%, when the transmission distance is 1 km. The results show that the same degree of turbulence and random jitter have different influences on the coupling efficiency of BG beams of different orders, and lower-order BG beams have better resistance to turbulence and jitter during propagation and coupling. Moreover, the effect of the guided mode field on the coupling efficiency and the resistance to turbulence varies for different values of mode radial index in the fiber p. The guided mode with p = 0 not only enables the BG beams of different orders to achieve the highest transmission efficiency in the coupling system almost simultaneously but also the random jitter and turbulence have less influence on the coupling efficiency of this mode. It means that the BG beams can have higher efficiency when coupled to the mode with p = 0 after long-distance transmission. This property of the fiber mode at p = 0 provides conditions for the simultaneous propagation of multiple BG beams in a parabolic fiber, which provides a theoretical basis for higher transmission capacity. This research work provides a theoretical model for the theoretical study of vortex beams and optical communication, which is beneficial for the design and application of vortex beams and has instructive meaning for practical engineering design.

Study on Flexural Behavior of Corroded I-Shaped Steel Beams Strengthened with Hybrid CFRP/GFRP Sheets.

How to effectively reinforce steel structures with rust and damage is an important research topic in the engineering field. This article takes the rusted I-beam as the research object and analyzes the effects of different CFRP/GFRP reinforcement methods on the bending performance of rusted I-beams through experimental research with a total of 1 unreinforced beam and 7 CFRP/GFRP-reinforced beams. The results show that when the number of CFRP/GFRP-reinforced layers is the same, replacing some of the CFRP with GFRP and using different interlayer mixed laying sequences have little effect on the bending bearing capacity of rusted I-beams. The number of CFRP/GFRP-reinforced layers is the key factor affecting the bending bearing capacity. At the same time, numerical simulation was conducted using finite element software to study the stress distribution and stress development law of the reinforced beam, and the numerical simulation results were consistent with the experimental results.

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

Cell invasion/migration through three-dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D-CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real-time, label-free, nondestructive, and high-throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D-CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti-tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D-CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.

Selective Valorization of Glycerol to Formic Acid on a BiVO4 Photoanode through NiFe Phenolic Networks.

The integration of the glycerol oxidation reaction (GOR) with the hydrogen evolution reaction in photoelectrochemical (PEC) cells is a desirable alternative to PEC water splitting since a large quantity of glycerol is easily accessible as the byproduct from the biodiesel industry. However, the PEC valorization of glycerol to the value-added products suffers from low Faradaic efficiency and selectivity, especially in acidic conditions, which is beneficial for hydrogen production. Herein, by loading bismuth vanadate (BVO) with a robust catalyst composed of phenolic ligands (tannic acid) coordinated with Ni and Fe ions (TANF), we demonstrate a modified BVO/TANF photoanode for the GOR with a remarkable Faradaic efficiency of over 94% to value-added molecules in a 0.1 M Na2SO4/H2SO4 (pH = 2) electrolyte. The BVO/TANF photoanode achieved a high photocurrent of 5.26 mA·cm-2 at 1.23 V versus reversible hydrogen electrode under 100 mW/cm2 white light irradiation for formic acid production with 85% selectivity, equivalent to 573 mmol/(m2·h). Transient photocurrent and transient photovoltage techniques and electrochemical impedance spectroscopy along with intensity-modulated photocurrent spectroscopy indicated that the TANF catalyst could accelerate hole transfer kinetics and suppress charge recombination. Comprehensive mechanistic investigations reveal that the GOR is initiated by the photogenerated holes of BVO, while the high selectivity to formic acid is attributed to the selective adsorption of primary hydroxyl groups in glycerol on TANF. This study provides a promising avenue for highly efficient and selective formic acid generation from biomass in acid media via PEC cells.

Extracellular Matrix Rigidities Regulate the Tricarboxylic Acid Cycle and Antibiotic Resistance of Three-Dimensionally Confined Bacterial Microcolonies.

As a major cause of clinical chronic infection, microbial biofilms/microcolonies in host tissues essentially live in 3D-constrained microenvironments, which potentially modulate their spatial self-organization and morphodynamics. However, it still remains unclear whether and how mechanical cues of 3D confined microenvironments, for example, extracellular matrix (ECM) stiffness, exert an impact on antibiotic resistance of bacterial biofilms/microcolonies. With a high-throughput antibiotic sensitivity testing (AST) platform, it is revealed that 3D ECM rigidities greatly modulate their resistance to diverse antibiotics. The microcolonies in 3D ECM with human tissue-specific rigidities varying from 0.5 to 20 kPa show a ≈2-10 000-fold increase in minimum inhibitory concentration, depending on the types of antibiotics. The authors subsequently identified that the increase in 3D ECM rigidities leads to the downregulation of the tricarboxylic acid (TCA) cycle, which is responsible for enhanced antibiotic resistance. Further, it is shown that fumarate, as a potentiator of TCA cycle activity, can alleviate the elevated antibiotic resistance and thus remarkably improve the efficacy of antibiotics against bacterial microcolonies in 3D confined ECM, as confirmed in the chronic infection mice model. These findings suggest fumarate can be employed as an antibiotic adjuvant to effectively treat infections induced by bacterial biofilms/microcolonies in a 3D-confined environment.

Milk Exosomes Facilitate Oral Delivery of Drugs against Intestinal Bacterial Infections.

Biopharmaceutics Classification System (BCS) class II and IV drugs exhibit low solubility and suffer a limitation in oral administration. Exosomes have attracted intensive attention in the efficient delivery of such compounds. However, low gastrointestinal stability and high production cost of exosomes hinder their development as drug carriers. Here, milk exosomes are functionalized with phosphatidylserine and are capable of improving the solubility of BCS class II and IV drugs, resulting in facilitating the oral delivery of the drugs. A natural flavonoid, α-mangostin, is loaded into exosomes (AExo) to enhance the antibacterial efficiency, demonstrated by clearing 99% of bacteria in macrophages. Furthermore, AExo exhibits high mucus penetrability and shows a significant therapeutic efficacy in two animal infection models. Collectively, this work expands the application of exosomes from bovine milk with simple operation and low cost, shedding light on the potential of milk exosomes in improving the solubility of drugs to enhance the efficacy of oral administration.

White blood cell count is not associated with flow-mediated vasodilation or nitroglycerine-induced vasodilation.

It is well known that white blood cell (WBC) count is an independent predictor of cardiovascular events. However, associations of WBC count and WBC subtypes with endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) are unclear. The aim of this study was to determine the relationships of WBC count and WBC subtypes with vascular function assessed by FMD and NID. A total of 1351 subjects in whom FMD and NID had been measured were recruited from Hiroshima University Vascular Registry. Mean values were 3.7 ± 2.8% for FMD and 11.8 ± 5.9% for NID. WBC was not correlated with FMD or NID. NID was significantly correlated with lymphocytes in univariate analysis but not with other hematologic parameters. In multiple linear regression analyses, NID was not correlated with lymphocytes. In all subgroups including subgroups of age, gender, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking and tertile of WBC count, WBC count was not correlated with FMD or NID. WBC count and WBC subtypes were not associated with endothelial function assessed by FMD or vascular smooth muscle function assessed by NID. WBC count and vascular function assessed by FMD and NID may reflect different aspects of atherosclerosis.Clinical Trial Registration Information: URL for Clinical Trial: http://www.umin.ac.jp Registration Number for Clinical Trial: UMIN000039512.

Self-reported total sitting time on a non-working day is associated with blunted flow-mediated vasodilation and blunted nitroglycerine-induced vasodilation.

We divided the 466 subjects into two groups based on information on sitting time on a non-working day and evaluated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID). FMD was smaller in subjects with sitting time on a non-working day of ≥6 h/day than in subjects with sitting time on a non-working day of <6 h/day (2.5 ± 2.6% vs. 3.7 ± 2.9%; p < 0.001). NID was smaller in subjects with sitting time at non-working day of ≥ 8 h/day than in subjects with sitting time on a non-working day of < 8 h/day (10.1 ± 5.6% vs. 11.5 ± 5.0%; p = 0.01). After adjustment for confounding factors for vascular function, the odds of having the lowest tertile of FMD was significantly higher in subjects with sitting time on a non-working day of ≥6 h/day than in subjects with sitting time on a non-working day of <6 h/day. The odds of having the lowest tertile of NID was significant higher in subjects with sitting time on a non-working day of ≥ 8 h/day than in subjects with sitting time on a non-working day of < 8 h/day. These findings suggest that prolonged sitting time on a non-working day is associated with blunted FMD and blunted NID.

Isolated diastolic hypertension is not associated with endothelial dysfunction.

Hypertension is associated with an impairment of endothelial function. However, it is unclear whether isolated diastolic hypertension is associated with endothelial dysfunction. The purpose of this study was to investigate the association of endothelial function with isolated diastolic hypertension diagnosed by using two major hypertension guidelines: systolic blood pressure (BP) < 130 mmHg and diastolic BP ≥ 80 mmHg according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline and systolic BP < 140 mmHg and diastolic BP ≥ 90 mmHg according to the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) hypertension guideline. We measured the flow-mediated vasodilation (FMD) of the brachial artery in subjects without systolic hypertension who were not treated with antihypertensive drugs. Of 3727 subjects (2813 men; mean age: 41.3 ± 10.9 years), 749 (20.1%) had isolated diastolic hypertension according to the 2017 ACC/AHA definition. Multiple logistic regression analysis revealed that isolated diastolic hypertension was not associated with endothelial dysfunction, defined as FMD < 7.0% (OR, 1.15; 95% CI, 0.98-1.35; P = 0.09). Of 4747 subjects (3727 men; mean age: 45.1 ± 10.8 years), 314 subjects (6.6%) had isolated diastolic hypertension according to the ESC/ESH definition. Multiple logistic regression analysis revealed that isolated diastolic hypertension was not associated with endothelial dysfunction after adjusting for age and sex (OR, 1.04; 95% CI, 0.82-1.32; P = 0.76). Isolated diastolic hypertension was not associated with endothelial dysfunction in individuals who were not treated with antihypertensive drugs regardless of the major hypertension guideline definition used.

Short stature is associated with low flow-mediated vasodilation in Japanese men.

An inverse association between height and the risk of cardiovascular disease has been reported. The objective of this study was to examine the association between height and endothelial function assessed by flow-mediated vasodilation (FMD). We evaluated cross-sectional associations of height with FMD in 7682 Japanese men. All participants were divided into four groups based on height: <155.0 cm, 155.0-164.9 cm, 165.0-174.9 cm, and ≥175.0 cm. Subjects in a lower quartile of FMD were defined as subjects having low FMD values. Univariate regression analysis revealed that height was significantly correlated with FMD (r = 0.14, p < 0.001). FMD values were 4.6 ± 3.1% in the <155.0 cm group, 5.2 ± 3.1% in the 155.0-164.9 cm group, 5.7 ± 3.1% in the 165.0-174.9 cm group and 6.1 ± 3.2% in the ≥175.0 cm group. FMD significantly increased in relation to an increase in height. Multiple logistic regression analysis revealed that higher height groups were significantly associated with a decreased risk of low FMD value compared with the <155.0 cm group after adjustments for age, presence of hypertension, dyslipidemia, diabetes, current smoking, and brachial artery diameter. FMD was low in subjects with a short stature compared with that in subjects with tall stature. Individuals with a short stature may require intensive interventions to reduce the risk of cardiovascular events.Clinical Trial Registration Information: URL for Clinical Trials: http://www.umin.ac.jp Registration Number for Clinical Trials: UMIN000012952.

Serum Potassium Levels of 4.5 to Less Than 5.0 mmol/L Are Associated with Better Vascular Function.

AIM: An experimental study showed that potassium inhibits the formation of reactive oxygen species by vascular cells. The purpose of this study was to investigate the association between serum potassium levels and vascular function. METHODS: We measured flow-mediated vasodilation (FMD) as an index of endothelial function in 3045 subjects (1964 men; mean age, 62.3±13.8 years) and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function in 1578 subjects (1001 men; mean age, 61.8±16.3 years). RESULTS: In the 3045 subjects, there was a significant positive correlation between FMD and serum potassium levels (r=0.09, P＜0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with FMD (ß=0.109, P＜0.001). When subjects were divided into two groups based on treatment with drugs that could alter serum potassium levels, the association between serum potassium levels and FMD was significant both in subjects with (ß=0.096, P＜0.001) and subjects without (ß=0.123, P＜0.001) treatment with drugs that could alter serum potassium levels. In the 1578 subjects, there was a significant positive correlation between NID and serum potassium levels (r=0.11, P＜0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with NID (ß=0.098, P＜0.001). The association between serum potassium levels and NID was significant both in subjects with (ß=0.121, P=0.001) and subjects without (ß=0.083, P=0.03) treatment with drugs that could alter serum potassium levels. CONCLUSIONS: Serum potassium levels of 4.5-＜5.0 mmol/L are associated with better vascular function regardless of the presence or absence of treatment with drugs that could alter serum potassium levels.

Relationship between hemoglobin A1c level and flow-mediated vasodilation in patients with type 2 diabetes mellitus receiving antidiabetic drugs.

AIMS/INTRODUCTION: Diabetes mellitus is associated with endothelial dysfunction. However, it is still controversial as to whether antidiabetic drug treatment affects endothelial function. The purpose of this study was to evaluate the relationships of the hemoglobin A1c (HbA1c) level with flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) in patients with type 2 diabetes mellitus who are receiving antidiabetic drugs. MATERIALS AND METHODS: The FMD was measured in 866 patients with type 2 diabetes mellitus who were receiving antidiabetic drugs (625 men and 241 women; mean age: 62 ± 10 years). The patients were divided into four groups according to HbA1c levels: <6.5, 6.5-6.9, 7.0-7.9, and ≥8.0%. RESULTS: There was an inverted U-shaped pattern of association of the HbA1c level with the FMD at an HbA1c level of about 7% of the peak of FMD in patients with type 2 diabetes mellitus who were receiving antidiabetic drugs. The FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5-6.9% group and the HbA1c 7.0-7.9% group (P < 0.001 and P < 0.001, respectively). The FMD values were similar in the HbA1c <6.5% group and HbA1c ≥8.0% group (P = 0.10). There were no significant differences in NID among the four groups (P = 0.98). CONCLUSIONS: These findings suggest that a low HbA1c <6.5% as well as a high HbA1c ≥8.0% is associated with endothelial dysfunction in patients with type 2 diabetes mellitus who are receiving antidiabetic drugs and that vascular smooth muscle function is similar in such patients regardless of the HbA1c level.

Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

The purpose of this study was to evaluate whether heart failure with mildly reduced ejection fraction (HFmrEF) is associated with vascular dysfunction and whether vascular function predicts future deterioration of LVEF in patients with HFmrEF. We evaluated endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) in 69 patients with HFmrEF and 426 patients without HF and evaluated the future deterioration of LVEF, defined as a decrease in LVEF to <40%, in 39 patients with HFmrEF for up to 3 years. Both FMD and NID were significantly lower in patients with HFmrEF than in patients without HF. We categorized patients into two groups based on low tertiles of NID: a low group (NID of <7.0%) and an intermediate and high group (NID of ≥7.0%). There were significant differences between the Kaplan-Meier curves for the deterioration of LVEF in the two groups (p < 0.01). Multivariate Cox proportional hazard analysis revealed that NID of <7.0% was an independent predictor of future deterioration of LVEF in patients with HFmrEF. Both endothelial function and vascular smooth muscle function are impaired in patients with HFmrEF compared with those in patients without HF. In addition, low NID of <7.0% predicts future deterioration of LVEF.